Tryptophan Fluoxetine

Several compounds affecting various 5-HT functional parameters (uptake inhibition (fluoxetine), metabolism (tranylcypromine) or synthesis (5-OH tryptophan, 5-HTP)) had no effect on subemetic doses of cisplatin [110]. In fact, tranylcypromine and 5-HTP antagonized emesis of cisplatin. Thus these results would favour an inhibitory role of 5-HT instead of emetogenic. It is conceivable that an excess of 5-HT may desensitize 5-HT3 receptors that may result in a reduced sensitivity to emetogenic stimuli. 

Figure 7. A serotonergic synapse including a depiction of the acute tryptophan depletion method discussed in the text. All large neutral amino acids (SLNAAs) share a common blood-brain barrier transporter. The serotonergic precursor, tryptophan, essentially competes with the other LNAAs for transport. Thus tryptophan is uniquely susceptible to acute dietary manipulation. Numerous serotonergic receptor types exist, including presynaptic S-HTm and (somatodendritic) 5-HTia autoreceptors and postsynaptic 5-HTia, 5-HTid, 5-HT2a 5-HT2c 5-HT3 and 5-HT4 receptors. Additional modulation of serotonin activity can occur via the action of selective serotonin re-uptake inhibitors (SSRls) including fluoxetine, fluvoxamine, and citalopram.

Sovner et al. (1998) have done an excellent job summarizing the data on antidepressants in patients with developmental disabilities. There have been nine reports of antidepressant use in adults with depression and MR and three reports of antidepressant use in children and adolescents. Eight of nine reports in adults were positive. The drugs studied included nialimide (n = 27), fluoxetine (9), imipramine (6), amoxapine (2), and nortriptyline (1) (total n = 45). In addition, Sovner et al. identified four reports of antidepressant use in children. One involved successful treatment with fluoxetine in an adolescent, another indicated efficacy with imipramine and amitriptyline in 9 of 12 children (Do-sen, 1982), and a third showed successful management in 3 of 4 children treated with imipramine or tryptophan plus nicotinamide (Dosen, 1990). One study of fluoxetine in depressed children with autism and MR witnessed improvement in depression but not in compulsive symptoms (Ghaziuddin and Tsai, 1991). 

The effects of a short-term tryptophan depletion were examined in 15 patients with OCD who had responded to treatment with various SRIs such as CMI, fluvoxamine, and fluoxetine. These patients underwent tryptophan depletion under double-blind, placebo-controlled conditions. Reduction of tryptophan had no significant effects on either obsessions or compulsions, but mean depression ratings were significantly increased during tryptophan depletion [Barr et al. 1994]. 

Steiner W, Eontaine R Toxic reaction following the combined administration of fluoxetine and L-tryptophan five case reports. Biol Psychiatry 21 1067-1071,... 

Delgado, P. L., Miller, H. L., Salomon, R. M., Licinio, J., Krystal, J. H., Moreno, F. A., Heninger, G. R., Chamey, D. S. 1999, Tryptophan-depletion challenge in depressed patients treated with desipramine or fluoxetine implications for the role of serotonin in the mechanism of antidepressant action, Biol.Psychiatry, vol. 46, no. 2, pp. 212-220. 

Delgado PL, Miller HL, Salomon RM, Licinio J, Krystal JH, 41. Moreno FA, Fleninger GR, Charney DS. Tryptophan-depletion challenge in depressed patients treated with desipramine or fluoxetine implications for the role of serotonin in the mechanism... 

Clinically important, potentially hazardous interactions with amitriptyline, amoxapine, bupropion, citalopram, clomipramine, desipramine, doxepin, fluoxetine, fluvoxamine, imipramine, meperidine, nefazodone, nortriptyline, paroxetine, pizotifen, protriptyline, rizatriptan, sertraline, sibutramine, sumatriptan, trimipramine, tryptophan, venlafaxine, zolmitriptan... 

Clinically important, potentially hazardous interactions with desvenlafaxine, dextromethorphan, dihydroergotamine, ephedra, ergot, fluoxetine, fluvoxamine, isocarboxazid, linezolid, lithium, MAO inhibitors, meperidine, methysergide, naratriptan, nefazodone, paroxetine, phenelzine, rizatriptan, sertraline, sumatriptan, tranylcypromine, tryptophan, venlafaxine, verapamil, zolmitriptan, zuclopenthixol... 

The symptoms of premenstrual syndrome (PMS), also called premenstrual dysphoric disorder, include depressed mood, anxiety, affective lability, and anger or irritability.79 Since low serotonin levels are thought to be involved in the etiology of depression, aggression, and impulsivity,80 specific serotonin reuptake inhibitors have been tested in PMS. The SSRI fluoxetine was found to be better than placebo.81 Since chronic treatment with SSRIs can influence many neuron systems other than serotonin,82 Steinberg et al.83 designed a study using tryptophan, relatively specific for its effect on serotonin, on the effects of symptoms of PMS. In a randomized controlled clinical trial, 37... 

Patients with unipolar depression are effectively treated with drugs, such as chlo-rimipramine and more recently fluoxetine, which are known to block neuronal uptake of serotonin. In addition, giving 5-hydroxy tryptophan (a precursor of serotonin) either alone or in combination with chlorimipramine seems to benefit these patients. 

Fluoxetine is absorbed well from the GI tract, is bound to plasma proteins to the extent of 95%, is metabolized in the Uver to norfluoxetine, and is excreted in the urine. Tryptophan is used as an antidepressant. However, the combined use of tryptophan, which increases the level of serotonin, and fluoxetine, which inhibits the neuronal uptake of serotonin, enhances the side effects of fluoxetine such as GI disturbances, anxiety, and insomnia (see Figure 86). 

B. lit addition, severe rigidity and hyperthermia may occur when patients receiving MAO inhibitors use therapeutic doses of meperidine (Demeroi), dextromethorphan, fluoxetine (Prozac), paroxetine (Paxii), sertraiine (Zoloft), ven-lafaxine (Effexor), or tryptophan the mechanism is unknown but may be related to inhibition of serotonin metabolism in the CNS, resulting in serotonin syndrome (see p 22). 

The manufacturers of duloxetine contraindicate the concurrent use of MAOIs because of the theoretical risk of the serotonin syndrome. Similarly they recommend caution with other serotonergic drugs, including the SSRIs, venlafaxine, and tryptophan. Fluvoxamine should not be used with duloxetine, because it markedly increases duloxetine levels. Low-dose paroxetine caused a modest increase in the duloxetine ATJC, and fluoxetine is predicted to interact similarly. 

A warning by the CSM in the UK about the risks of giving fluvoxamine with tryptophan appears to be an extrapolation from the serious reaction (the serotonin syndrome) which has been seen with fluoxetine (see above). 

Tryptophan is a precursor of serotonin (5-hydroxytryptamine) and the authors point out that the symptoms resemble the serotonin syndrome, which occurs when serotonin levels are increased. They warn against the concurrent use of tryptophan with fluoxetine or other serotonin reuptake inhibitors. This caution is echoed by most of the manufacturers of the SSRIs the UK manufacturer of paroxetine additionally mentions oxitriptan [L-5-hydroxytryptophan]... 

Levitan RD, Shen J-H, Jindal R, Driver HS, Kennedy SH, Shapiro CM. Preliminary randomized double-blind placebo-conttolled trial of tryptophan ccmbined with fluoxetine to treat major depressive disorder antidepressant and hjfpnotic effects. JPsychiatry Neurosci (2000)... 

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